Tetrahydrofuran → 3-[2-((R)-6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-oxazolidine-2,4-dione

HRID 251873Notes

Reaction equation

HRID 251873 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][C@H:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][C:21](=[O:24])[CH2:22][OH:23].C[Si](C)(C)[N-][Si](C)(C)C.[Na+].C1C[O:38][CH2:37]C1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][C@H:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N:20]1[C:21](=[O:24])[CH2:22][O:23][C:37]1=[O:38]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 59682845N-[2-((R)-6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-2-hydroxyacetamide

Product 1

HCID 117180843-[2-((R)-6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-oxazolidine-2,4-dione

Procedure

N-[2-((R)-6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]-2-hydroxy-acetamide (20 mg) was dissolved in absolute THF (2 ml), and reacted at room temperature with sodium hexamethyldisilazide solution (0.5 ml; 2 M in THF) with stirring. Afterward, 1,1-carbonyldiimidazole (13 mg) was added and the mixture was stirred at room temperature for 2 h. After standing overnight, the reaction mixture was concentrated, the residue was dissolved in ethyl acetate/water and basified with sodium hydrogencarbonate solution, and the phases were separated. The aqueous phase was extracted three times with ethyl acetate. The combined extracts were dried with magnesium sulfate, filtered and concentrated. The residue was purified by means of preparative HPLC. The fractions comprising product were combined, the acetonitrile was removed on a rotary evaporator, and the aqueous residue was neutralized with saturated sodium hydrogencarbonate solution and extracted three times with ethyl acetate. After the combined ethyl acetate phases had been dried over magnesium sulfate, they were filtered and concentrated to dryness. The residue was dissolved in water/acetonitrile and the clear solution was freeze-dried overnight. 10 mg of the desired product were obtained.

Workup

  1. stirringthe mixture was stirred at room temperature for 2 h
  2. concentrationthe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in ethyl acetate/water
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted three times with ethyl acetate
  6. dry with materialThe combined extracts were dried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by means of preparative HPLC
  10. customthe acetonitrile was removed on a rotary evaporator
  11. extractionextracted three times with ethyl acetate
  12. dry with materialAfter the combined ethyl acetate phases had been dried over magnesium sulfate, they
  13. filtrationwere filtered
  14. concentrationconcentrated to dryness
  15. dissolutionThe residue was dissolved in water/acetonitrile
  16. customthe clear solution was freeze-dried overnight

Sources & evidence

ORD record
ord-3c69419f07f648ac997e8f96f7930af6
Source dataset
uspto-grants-2011_01
Patent number
US07868003B2

Reaction notes

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